The present invention relates to method and apparatus for the thermal ablation of the interior lining of an organ, and more particularly for destruction of Barrett""s tissue and other lesions of the gastrointestinal tract by cryo-ablation of the gastrointestinal mucosa (gastrointestinal tract lining).
Barrett""s esophagus is a recognized precursor to 50% of all esophageal cancers. The incidence of esophageal cancer is rising and this disease is now among the top 15 cancers (Blot et al, JAMA, 270:1320 [1993]). Barrett""s tissue has been found in 10% of an asymptomatic population undergoing upper gastrointestinal endoscopy.
Standard therapy for esophageal cancer is removal of the esophagus, with mortality rates up to 37%. Treatment of this cancer costs $25,000 to $50,000 dollars per patient.
Barrett""s esophagus is characterized by abnormal cell growth along the inner lining of the esophagus above the lower esophageal sphincter. Recent studies have demonstrated that when the metaplastic columnar epithelium characteristic of Barrett""s is removed, healing replaces the Barrett""s tissue with normal stratified squamous epithelium (Sampliner et al, Gastrointestinal Endoscopy, 44:532-535 [1966]). This presumably reduces the risk of cancer.
Lives would be saved if Barrett""s tissue could be removed quickly, inexpensively, and with low risk. However, the only available procedures have been slow, costly, uncomfortable, and/or dangerous. As a result, Barrett""s esophagus goes untreated in many patients, whose health suffers.
The known ablation treatments for Barrett""s esophagus include laser treatment (Ertan et al, Am. J. Gastro., 90:2201-2203 [1995]), ultrasonic ablation (Bremner et al, Gastro. Endo., 43:6 [1996]), photodynamic therapy (PDT) using photo-sensitizer drugs (Overholt et al, Semin. Surq. Oncol., 1:372-376 (1995)), and multipolar electrocoagulation such as by use of a bicap probe (Sampliner et al, supra). The treatments are often made with the aid of an endoscope.
Both sonic and light treatments require expensive apparatus and treat only a small area at one time, so that an operation to remove the Barrett""s tissue becomes tedious as well as more costly. One reported treatment with Nd:YAG laser used a 2.2-mm beam to treat large areas of the esophagus (Ertan et al, Am. J. Gastro. 90:2201-2203 [1995]). Furthermore, such therapies are often accompanied by esophageal strictures and significant patient inconveniences; since total avoidance of sun exposure and bright light is required for one month after photodynamic therapy.
Another problem is that there is no visual indication of which tissues have been treated, or the extent to which tissues have been treated. The physician, looking through an endoscope, cannot see the effects of the sound or light directly.
Cryotherapy of the esophagus via direct contact with a liquid nitrogen cryoprobe (metal probe cooled to a low temperature) has been studied in both animal models and humans (Rodgers et al, Cryobiology. 22:86-92 (1985); Rodgers et al, Ann. Thorac. Surq., 55:52-7 [1983]) and has been used to treat early esophageal cancer (Grana et al, Int. Surg., 66:295 [1981]). Disadvantages of this modality include the necessity for direct mucosal contact, which temporarily binds the probe to the esophagus, potentiating the risk of esophageal perforation and inability to control the exact area of mucosal ablation. Rodgers et al states that a cryoprobe must include a heating element to allow it to be removed. This precludes removal of the probe until thawing has occurred. The depth of the injury with a solid cryoprobe cannot be reliably controlled. If the tip heater malfunctions, or timing is not precise, the depth of freezing can become dangerous. In spite of the heating element, cats died from esophageal lesions in some cases, apparently caused by freezing too deeply and destroying the esophageal wall entirely. These studies highlight the fact that controlling the amount of tissue that is irreversibly damaged by cooling is one of the main problems with cryosurgery.
Use of a bicap electrocoagulation probe has been suggested as a means for ablation of Barrett""s esophagus (Heier et al, Gastro. Endo., 43:185 [1996]). The use of a bicap electrocoagulation probe also suffers from many disadvantages. Since the tip is small and must be repeatedly energized, the operation will be slow and time-consuming. Furthermore, the depth of injury is difficult to control. Esophageal perforation could occur with excessive duration of the electrocautery current.
All the known ablation treatments using sound, light, or heat also suffer from another defect, a defect common to all: penetration of the damage. The treatments cannot be adjusted to destroy only the very thin lining with the Barrett""s tissue; underlying tissue is destroyed as well.
As flesh is somewhat transparent to both sound and light, these energies will penetrate some distance below the surface. The proportion of energy absorbed by the tissue is generally constant, and so, at least to a first approximation, the intensity of the light or sound will fall off exponentially with depth. Therefore, the amount of tissue damage will also tend to decrease exponentially with distance. There is consequently no sharp line of demarcation between destroyed tissue and tissue which is not affected: the degree of damage decreases continuously. Healthy tissue is damaged along with diseased tissue.
The same type of damage results from heat probe or cryoprobe treatments. When the surface temperature of flesh is raised, heat travels by conduction into the tissue. The penetration of the heatxe2x80x94the temperature/depth functionxe2x80x94depends on the surface temperature, the exposure time, and the heat capacity of the hot probe in contact with the surface. The degree of damage at any one depth depends on the temperature reached. Similar problems are involved with the freezing associated with contact by a solid cryoprobe.
Clearly, to raise the tissue temperature to a damaging level in only a thin layer of epithelium, heat must be applied quickly from a very high-temperature probe. However, this creates problems of possible sticking and require precise timing of the hot probe contact duration, lest heat penetrate too deeply.
Complicating the use of heat, there is also a time factor. Not only the peak temperature reached by tissue, but also how long the tissue xe2x80x9cbakesxe2x80x9d at the high temperature, determines the amount of damage. (This is the reason cold water should be put onto a burn, even after the bum is away from heat.)
With none of the existing therapies is one able to precisely control the depth of tissue damage while maintaining a sharp demarcation between damaged and undamaged tissue, with the physician being able to observe the precise location and degree of damage as it occurs. Ideally, the Barrett""s tissue should be destroyed with the direct visualization and control by physician in a manner which avoids any substantial damage to adjacent healthy tissue.
The present invention overcomes the drawbacks of the prior art by using a direct spray of cryogenic liquid to ablate Barrett""s tissue in the esophagus. Liquid nitrogen, an inexpensive and readily available liquified gas, is directed onto the Barrett""s tissue through a tube while the physician views the esophagus through an endoscope. The apparatus and method of the present invention can be used to cause controlled damage to the mucosal layer at any location in the gastrointestinal tract in a manner in which re-epithelialization can occur. They can be used not only for the treatment of Barrett""s esophagus, which is the preferred application of the present invention, but also for the treatment of any mucosal gastrointestinal lesion, such as tumor, polyps and vascular lesions. The apparatus and method can also be used for the treatment of the mucosal layer of any luminal area of the body which can be reached by an endoscope.
Liquid nitrogen spray has several distinct advantages over the prior art:
1) As compared to some of the prior art therapies, there is a sharp demarcation between damaged tissue and non-damaged tissue. Above the freeze surface, all the cells are killed; below, they are not harmed. Thus, it is possible to ablate the Barrett""s, or other gastrointestinal tract lesions, without damaging the underlying tissues. This minimizes both the trauma and the risk of infection.
2) Unlike a solid cold probe, liquid nitrogen cannot stick to tissue and cause severe frostbite.
3) The layer of destroyed tissue is thinner than with previous therapies, including solid-probe cryotherapy, and this again minimizes the damage as compared to the prior art. The reason that the liquid nitrogen spray can freeze a thinner layer than prior-art therapies is that it instantly boils when it touches flesh, because the temperature difference is usually more than 200xc2x0 C. Liquids have high thermal conductivities, and to boil a liquid requires large amounts of heat (the latent heat of vaporization). These two factors together mean that heat is removed from the surface of the tissue at an extremely high rate, and because of this rapid surface cooling the freezing depth can be very shallow. The temperature differential in the flesh is much higher than it is with a hot metal probe because heat does not need to travel through a metal; the temperature is generated at the surface itself As a result, the tissue surface can be frozen to well below zero before the tissue just under that frozen tissue has a chance to appreciably drop in temperature.
4) Freezing kills cells, but connective tissue and other body substances are not damaged. Thus, the trauma is less as compared to heat burns. Shepherd et al, Cryobiology, 21:157-169 [19841]).
5) The cryoablation procedure requires only 15-20 minutes. Animal studies have been done both under general anesthesia and under conscious sedation. Thus, the procedure can be performed on adult humans with a local anesthetic or possibly without any anesthetic at all. Freezing is less painful than other methods of killing tissue because cold inherently anesthetizes the nerves. As the operation of the present invention can be performed without general anesthesia, the cost and danger are both reduced still further over treatments employed by the prior art.
6) The cost of the procedure is minimal compared to that of the prior art, not only because of the short time for the operation and the relative safety (reducing insurance costs) but also because the capital cost is relatively low. No special medical grade of liquid nitrogen is required. A storage canister can presently be refilled with liquid nitrogen by a commercial gas service for a delivery fee of approximately $20, plus about $3 per liter for the liquified nitrogen itself. One treatment will use approximately a liter or less. The cost for nitrogen can be as low as $30 per month even if only one treatment is performed during that period.
7) The procedure can be conducted in such a manner as to allow constant visualization by the physician of the tissue damage as it occurs. Means are provided for removal of moist air at the distal end of the endoscope while dry nitrogen is sprayed. Thus, fogging of the endoscope lens can be substantially avoided, allowing clear observation of the procedure as it occurs.
In order to realize the benefits of liquid nitrogen spray in the esophagus, the present invention provides these features:
(1) A standard xe2x80x9cdiagnosticxe2x80x9d endoscope can be used, which is almost universally available to medical personnel, although a standard xe2x80x9ctherapeuticxe2x80x9d endoscope can also be used. These relatively expensive pieces of equipment need not be purchased for the procedure.
(2) The endoscope allows the physician to see inside the esophagus and direct the spray of nitrogen. Unlike prior-art therapies, the present invention allows the physician to see what areas have been frozen to a low temperature because the esophageal wall frosts and turns white. The frosting lasts for several seconds because the entire inside of the esophagus is at a low temperature, hovering near freezing during the operation. This is due to the large amounts of cold nitrogen gas generated by boiling of the liquid nitrogen. Thus, it is possible for the physician not only to know what areas are frozen, but what areas have been frozen recently. This allows a systematic progress of cryotherapy over the area of Barrett""s tissue without over-freezing or non-freezing of any area.
(3) The endoscope can be disposed with fiberoptics, a T.V. camera and a display screen to allow the surgeon to view the treatment and treated area of the esophagus.
(4) The liquid nitrogen delivery equipment can be very inexpensive by medical standards. Nitrogen may be delivered through a catheter of standard flexible tubing, such as TEFLON tubing. Plastic tubing is universally available, inexpensive, and safe because of its low thermal conductivity, which prevents the tubing from sticking to the esophageal wall. Other materials superior to TEFLON could be used.
(5) The flow of nitrogen can be controlled by a simple, reliable, and low-cost delivery system. The nitrogen container is pressurized to push the liquid through the catheter. In one embodiment of this invention, the flow is hand-controlled by the pressure via a valve located at the nitrogen storage container. If more precise control is needed, the liquid nitrogen may be pumped directly or the flow may be controlled by a valve close to the proximal end of the catheter. As an example, a solenoid valve can be used.
(6) If a more rapid delivery of liquified gas is required, a pressure building tube or coil for supplying heat can be provided on the nitrogen container or tank. Actuating this pressure building coil causes the liquid nitrogen to build up pressure in the container thus allowing the nitrogen to be more rapidly delivered to the catheter.
(7) During cryosurgery, the invention provides for removal of gas generated by the brisk boiling of liquid nitrogen. Removal is necessary for several reasons: first, the gas will build up a dangerous pressure if there is no escape path; second, the gas will tend to enter the stomach and bloat it because the esophagus is at least partially blocked by the endoscope, and the lower gastrointestinal tract presents a path of lessened resistance; third, the gas boiled off from the esophageal surface may be at a sub-zero temperature and should be removed to prevent over-freezing; and fourth, the initially moist air can be removed so as to avoid substantial condensation on the endoscope lens.
(8) The inventors have found that in using the cryospray in the relatively enclosed esophageal cavity the pressure of the spray is to be reduced. If the pressure is not reduced, the high volume of gas could unduly expand in the esophageal cavity and cause patient discomfort and/or rupture of vital tissue. In order to produce a cryogenic spray of reduced pressure, this invention proposes a vent between the gas supply tank and the catheter. Other methods for reducing pressure are envisioned by this invention.
(9) Importantly, the catheter is supplied attached to a vent. A catheter, not supplied with such a vent, will deliver a high pressure spray which could be injurious to internal tissue. As pointed out, methods other than a vent could be used to reduce pressure.
(10) The catheter employed by this invention is made of a material which is not brittle, such as PTFE and polyamide. In addition, the catheter is to be insulated. The catheter is designed to withstand extremely cold temperatures without becoming stiff and brittle and without affecting inherent flexibility and maneuverability of the endoscope. For example, the insulated catheter should be capable of withstanding temperatures down to xe2x88x92100xc2x0 C. The temperature of gas sprayed at the tip is approximately between xe2x88x9220xc2x0 C. to xe2x88x9250xc2x0 C. However, higher and lower temperatures are contemplated by the inventors.
(11) The invention herein disclosed contemplates treating precancerous lesions.
The herein disclosed invention contemplates treating various internal lesions with a low pressure cryogenic spray. Low pressure can be determined by routine experiment by those skilled in the art. The inventors have found a pressure of approximately 3-5 psi to be operative. In addition, pressures up to around 45 psi would be effective.